NUDT15 R139C causes thiopurine-induced early severe hair loss and leukopenia in Japanese patients with IBD
NUDT15 R139C causes thiopurine-induced early severe hair loss and leukopenia in Japanese patients with IBD
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DOI：
10.1038/tpj.2015.43
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发表时间：
2016-06-01
影响因子：
2.8
通讯作者：
Shimosegawa, T.
中科院分区：
文献类型：
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作者：
Kakuta, Y.;Naito, T.;Shimosegawa, T.
硫嘌呤（包括硫唑嘌呤 (AZA) 和 6-巯基嘌呤 (6MP)）的疗效已被证明可用于治疗炎症性肠病 (IBD)。使用医生改变的硫嘌呤治疗最常见和最严重的不良事件是白细胞减少症。脱发也是一种严重的事件，可能是患者拒绝硫嘌呤治疗的关键原因。硫嘌呤引起的严重脱发会导致美观问题，并且需要很长时间才能恢复。在最近的一项研究中，NUDT15 R139C 与韩国和高加索人群中硫嘌呤诱导的白细胞减少症密切相关。在这项研究中，我们进行了一项关联研究，以调查和复制 R139C 与日本患者硫嘌呤不良事件的关联。共有 142 名有硫嘌呤治疗史的日本 IBD 患者接受了检查。使用定制的 TaqMan 基因分型测定对 NUDT15 R139C 进行基因分型。从病历中审查了包括白细胞减少在内的不良事件。通过乘以 2 作为硫嘌呤剂量，将 6MP 剂量调整为 AZA 当量。 5 名患者出现严重脱发，且全部为 R139C 风险纯合子 (T/T)。在 C/T 或 C/C 基因型患者中未观察到早期严重脱发（P = 3.82 x 10(-16)，比值比 = 212）。 R139C 与早期 (
The efficacy of thiopurines, including azathioprine (AZA) and 6-mercaptopurine (6MP), has been demonstrated for the treatment of inflammatory bowel disease (IBD). The most common and serious adverse event of treatment with thiopurines altered by doctors is leukopenia. Hair loss is also a serious event that could be a critical reason for patients to decline thiopurine treatment. Thiopurine-induced severe hair loss causes cosmetic problems, and it takes a long time to recover. In a recent study, NUDT15 R139C was strongly associated with thiopurine-induced leukopenia in Korean and Caucasian populations. In this study, we performed an association study to investigate and replicate the association of R139C with adverse events of thiopurines in Japanese patients. A total of 142 Japanese patients with IBD, with histories of thiopurine treatment, were examined. NUDT15 R139C was genotyped using a custom TaqMan genotyping assay. Adverse events including leukopenia were reviewed from medical records. The 6MP dose was adjusted to AZA equivalents by multiplying with 2 as a thiopurine dose. Five patients developed severe hair loss and all of them were risk homozygous (T/T) for R139C. No early severe hair loss was observed in patients with the C/T or C/C genotype (P = 3.82 x 10(-16), odds ratio = 212). The association of R139C with early (